What is the differential diagnosis (DDX) and treatment approach for a young adult patient experiencing panic attacks, considering potential underlying psychiatric, medical, or substance-related causes?

Differential Diagnosis of Panic Attacks

Rule out medical conditions first—hyperthyroidism, hypoglycemia, cardiac arrhythmias, and substance-induced causes are the most critical mimics that must be excluded before confirming a psychiatric diagnosis. 1, 2

Medical Conditions That Mimic Panic Attacks

Before diagnosing panic disorder, systematically exclude these medical causes:

Endocrine and Metabolic

• Hyperthyroidism: Excessive thyroid hormone directly causes anxiety symptoms including palpitations, tremor, and sweating 1, 2
• Hypoglycemia/Diabetes: Blood sugar fluctuations trigger panic-like symptoms with autonomic activation 2
• Order thyroid function tests and glucose levels if clinical presentation suggests these conditions 1

Cardiovascular

• Cardiac arrhythmias: Palpitations and chest discomfort can initiate or mimic panic attacks 2
• Distinguish from panic by: ECG findings, relationship to exertion, and absence of psychological triggers 3

Respiratory

• Asthma: Shortness of breath and respiratory distress overlap significantly with panic symptoms 2

Neurological

• Migraines: Can present with anxiety and autonomic symptoms 2
• Seizures: Distinguished by prolonged tonic-clonic movements (>15 seconds) that coincide with loss of consciousness, post-ictal confusion, and tongue biting 3

Substance-Related Causes

• Caffeine excess: Directly provokes anxiety and panic 2
• Medications: Many prescription drugs induce anxiety as a side effect 2
• Illicit stimulants: Cocaine, amphetamines trigger panic symptoms 2
• Alcohol/substance withdrawal: Creates rebound anxiety and panic 2

Psychiatric Differential Diagnosis

Once medical causes are excluded, consider these psychiatric conditions:

Primary Anxiety Disorders

• Panic Disorder: Recurrent unexpected panic attacks with abrupt surge of intense fear, physical manifestations (palpitations, sweating, trembling, shortness of breath, chest pain, dizziness), and anticipatory anxiety about future attacks 4, 5
• Generalized Anxiety Disorder (GAD): Chronic, pervasive worry about multiple topics with physical symptoms, but lacks discrete panic attacks 4, 1
• Social Anxiety Disorder: Panic occurs specifically in social situations with fear of negative evaluation 4
• PTSD: Panic symptoms triggered by trauma reminders 2

Mood Disorders

• Major Depressive Disorder: 56% of patients with depression have comorbid anxiety, significantly increasing suicide risk 2
• Bipolar Disorder: Extreme anger bursts and projection may indicate comorbid mood disorder 1
• Assess for depressive symptoms: anhedonia, guilt, worthlessness, suicidal ideation 3

Other Psychiatric Conditions

• Obsessive-Compulsive Disorder: Anxiety related to obsessions and compulsions 3
• ADHD: Comorbid in many anxiety presentations 3, 2
• Eating Disorders: Frequently co-occur with anxiety 3, 2
• Substance Use Disorders: Often present concurrently and must be treated simultaneously 6

Somatization and Conversion

• Somatization Disorder: Mimics syncope and panic; patients may faint with witnesses present without injury 3
• Conversion Reactions (Hysteria): Loss of consciousness in presence of witness without typical panic features 3

Psychosocial Triggers and Risk Factors

Trauma and Stressors

• Sexual harassment, assault, and trauma: Common underlying triggers, particularly in women 2
• Stressful life events: Directly precipitate anxiety episodes 2
• Insecure attachment patterns: Increase vulnerability 2

Developmental Vulnerabilities

• Behavioral inhibition in childhood: Temperamental fearfulness predicts later anxiety 2
• Autonomic hyperreactivity: Exaggerated physiological stress responses 2
• Family history: 30-50% heritability indicates genetic vulnerability 2

Age-Specific Considerations

• Adolescents/Young Adults: Panic and agoraphobia typically onset in later adolescent/young adult years 3
• Pregnancy/Postpartum: Anxiety disorders increase in frequency and severity during this period 2

Key Diagnostic Features of Panic Disorder

A panic attack reaches peak intensity within 10 minutes and includes at least 4 of these symptoms: 5, 7

• Palpitations or accelerated heart rate
• Sweating
• Trembling or shaking
• Shortness of breath or smothering sensation
• Feeling of choking
• Chest pain or discomfort
• Nausea or abdominal distress
• Dizziness, lightheadedness, or faintness
• Derealization or depersonalization
• Fear of losing control or "going crazy"
• Fear of dying
• Paresthesias (numbness/tingling)
• Chills or hot flushes

Panic Disorder diagnosis requires: 5

• Recurrent unexpected panic attacks
• At least one attack followed by ≥1 month of: persistent concern about additional attacks, worry about implications/consequences, or significant behavioral change related to attacks

Critical Red Flags Requiring Immediate Attention

• Suicidal ideation or self-harm behaviors 4
• Severe agitation 4
• Comorbid depression (especially GAD with depression—greatest suicide risk) 3, 4
• Psychotic symptoms 4
• Substance use as self-medication 4

Common Diagnostic Pitfalls to Avoid

• Missing medical mimics: Always check thyroid, glucose, and cardiac function 4, 1
• Overlooking comorbidities: Depression, ADHD, eating disorders, and substance use frequently co-occur 4
• Dismissing symptoms as "just stress": Panic disorder causes severe impairment and suicide risk 4
• Relying solely on patient report: Use multi-informant approach when possible 4
• Attributing all anxiety to psychiatric causes: Maintain high suspicion for medical conditions 3, 1

Validated Screening Tools

• GAD-7: For generalized anxiety screening in patients ≥8 years 4, 6
• SCARED: Screen for Anxiety Related Emotional Disorders 4
• Patient Health Questionnaire for Panic Disorder: Validated for PD screening 6

Treatment Approach

First-Line Pharmacological Treatment

Initiate an SSRI as first-line medication for panic disorder: 1, 8, 5

• Sertraline: Start 25 mg/day for first week, then 50-200 mg/day (mean effective dose 131-185 mg/day) 8
• Paroxetine: Effective for panic disorder with demonstrated long-term relapse prevention 5
• Fluoxetine: Strong evidence of efficacy 7

Benzodiazepines: Limited Role

Benzodiazepines are NOT recommended for first-line or long-term use due to dependence risk and higher mortality 6. However, they show efficacy for acute management: 7

• Alprazolam and clonazepam: Most effective for reducing panic attack frequency and ranked highest for tolerability 7
• Diazepam: Strong evidence for efficacy and low dropout rates 7
• Use only for short-term bridging while SSRIs take effect 3, 6

Psychological Treatment

Cognitive-behavioral therapy (CBT) should be initiated concurrently with medication: 1

• Combination of CBT + SSRI is superior to either alone 1
• Provides durable skills that may prevent relapse after medication discontinuation 1
• Graded self-exposure based on CBT principles for PTSD symptoms 3

Treatment Duration

• Continue antidepressant for 9-12 months after recovery to prevent relapse 3
• Long-term maintenance demonstrated in relapse prevention trials for both panic disorder and OCD 8, 5

Monitoring Schedule

Follow-up at 2 weeks, then monthly for first 3 months: 1

• Monitor for worsening anxiety/panic
• Assess for suicidal ideation (especially in adolescents/young adults)
• Check medication adherence
• Evaluate response: reduction in panic frequency, improved sleep, decreased worry, better functional capacity 1

Comorbidity Management

Treat substance use disorders concurrently with anxiety disorder 6. For comorbid depression, anxiety, or other psychiatric conditions, multifaceted treatment plans are necessary 3.